Hormones
Poly(amino acids) which have been used or proposed to be used for pharmaceutical or veterinary purposes include, but are not limited to the following, including synthetic, natural or recombinant sources thereof: polypeptide hormones such as calcitonins, e.g. salmon calcitonin, growth hormone, including human growth hormones (hGH), recombinant human growth hormones (rhGH), bovine growth hormones, and porcine growth hormones; growth hormone-releasing hormones and pituitary thyroid hormone.
The parathyroid hormone or PTH can be the full length, 84 amino acid form of parathyroid hormone, e.g. the human form, hPTH (1-84), or any polypeptide, protein, protein fragment, or modified fragment, i.e. PTH-related peptides and PTH analogs, capable of mimicking the activity of hPTH (1-84) in controlling calcium and phosphate metabolism to build bone in the human body. The PTH fragments will generally incorporate at least the first 28 N-terminal residue and include by way of example PTH (1-28), PTH (1-31), PTH (1-34), PTH (1-37), PTH (1-38) and PTH (1-41) and analogues thereof, e.g. PTS893. The PTH can be a single PTH or any combination of two or more PTHs.
The preferred PTH fragment is PTH (1-34).
These parathyroid hormones are commercially available or can be obtained recombinantly, by peptide synthesis, or by extraction from human fluid by methods well established in the art.
The amount of PTH to be administered is generally an amount effective to stimulate new bone formation i.e. a therapeutically effective amount. This amount will necessarily vary with the age, size, sex and condition of the subject to be treated, the nature and severity of the disorder to be treated and the like. However, the unit amount can be less than the described dosage when a plurality of the compositions are to be administered, i.e., the total effective amount can be administered in cumulative dosage units. The unit amount of PTH can also be more than the effective amount when the composition provides sustained release of the pharmacologically active agent. The total amount of PTH to be used can be determined by methods known to those skilled in the art. However, in general, satisfactory results will be obtained systemically at daily dosages of from about 0.001 μg/kg to about 10 mg/kg animal body weight, preferably 1 μg/kg to about 6 μg/kg body weight.
The preferred pharmacologically active agent is a pharmacologically active peptide, particularly calcitonin. A known class of pharmacologically active agents, calcitonins have varying pharmaceutical utility and are commonly employed in the treatment of e.g. Paget's disease, hypercalcemia and postmenopausal osteoporosis. Calcitonins, e.g. salmon, (Asu1-7)-eel or human calcitonin, are compounds which are long-chain polypeptide hormones secreted by the parafollicular cells of the thyroid gland in mammals and by the ultimobranchial gland of birds and fish. Various calcitonins, including salmon, pig and eel calcitonin are commercially available and commonly employed for the treatment of e.g. Paget's disease, hypercalcemia of malignancy and osteoporosis. The calcitonin can be any calcitonin, including natural, synthetic or recombinant sources thereof, as well as calcitonin derivatives such as 1,7-Asu-eel calcitonin. The compositions can comprise a single calcitonin or any combination of two or more calcitonins. The preferred calcitonin is synthetic salmon calcitonin.
The calcitonins are commercially available or may be synthesized by known methods.
The amount of pharmacologically active agent is generally an amount effective to accomplish the intended purpose, e.g. a therapeutically effective amount. However, the unit amount can be less than the described dosage when a plurality of the compositions are to be administered, i.e., the total effective amount can be administered in cumulative dosage units. The unit amount of active agent can also be more than the effective amount when the composition provides sustained release of the pharmacologically active agent. The total amount of active agent to be used can be determined by methods known to those skilled in the art. However, because the compositions may deliver the active agent more efficiently than prior compositions, less amounts of active agent than those used in prior dosage unit forms or delivery systems can be administered to a subject while still achieving the same blood levels and/or therapeutic effects.
The appropriate dosage of calcitonin to be administered will, of course, vary depending upon, for example, the amount of calcitonin to be administered and the severity of the condition being treated. However, in general, satisfactory results will be obtained through systemic intranasal or injectable administration at daily dosages of from about 0.5 μg/kg to about 10 μg/kg animal body weight, preferably 1 μg/kg to about 6 μg/kg body weight.
Human Growth Hormone (hGH) (or somatotropic hormone or somatotropin) is a polypeptide hormone secreted by the anterior lobe of the pituitary gland that promotes growth of the body, especially by stimulating release of somatomedin, and that influences the metabolism of proteins, carbohydrates, and lipids.
Included under the hGH definition may also be any of various natural or synthetic substances that regulate the growth of animals or plants, such as pituitary growth hormone in vertebrates and auxins in plants.
Bone Disorders
Many types of bone disorders are known. A first class of disorders fall in the class relating to disorders caused by bone resorption. Examples of such disorders are osteoporosis, osteolyisis and Paget's disease.
In a second class of disorders are arthritic conditions. An example of such disorders is osteoarthritis.
New Formulations
There have been many attempts to promote absorption of poly (amino acids) such as peptide and proteins, e.g. hormones. It is generally believed that peptides and proteins need to be protected from the gastric and intestinal environment, where many peptidases exist and significant degradation may occur. Enteric coating and the addition of peptidase inhibitors to pharmaceutical compositions have proven to be effective in improving poly(amino acid), e.g. protein and peptide, absorption via oral administration.
However, those approaches alone do not offer sufficient protection to achieve a satisfactory plasma level of the peptide and proteins, there still remains a need to provide alternative means for successfully delivering peptide and protein medicaments to a patient, whilst protecting them from chemical and enzymatic degradation in order to enable them to provide a therapeutic effect.
This is particularly the case for calcitonins, where oral administration is the preferred delivery route since it is convenient, relatively easy and generally painless, resulting in greater patient compliance relative to other modes of delivery.